Human Cytomegalovirus (HCMV) also known as cellular inclusion body virus is named for the swelling of infected cells and the possession of huge intranuclear inclusions. The HCMV belongs to β herpes virus subfamilies, with the diameter of about 200 nm, is one of the largest animal viruses, and has a 64 nm inner core containing virus DNA, with a 110 nm icosahedrons coated outside. An integrated particle is wrapped by an envelope in which BJ consists of protein or glycoprotein encoded by 25-30 virus particles at least. The HCMV has the genome length of 235-240 kb and the molecular weight of 150-160*103 kDa as well as linear double-stranded DNA, and belongs to DNA viruses. HCMV consists of long (L) and short (S) compositions or segments. Due to different directions or inversion at the mutual junction of the two compositions, the structures of DNA molecules have 4 homogenous isomers. Because of its wide distribution, other animals can be infected to cause various kinds of system infection from slight asymptomatic infection to serious defects or death mainly based on a genitourinary system, a central nervous system and liver diseases.
An HCMV gene structurally contains polypeptide segments encoding 3 infection cell specificities, namely an immediate early protein region, an early protein region and a later protein region, with 3 kinds of protein having immunogenicity and time phases. HCMV transcription-translation is regulated and controlled by HCMV and host cells. The expression of immediate early genes and early genes is regulated and controlled by promoters, which are commonly detected as acute infection. The transcription and translation of later genes are regulated and controlled by IE and E genes and protein, which marks the incubation period of viruses after detection. The maturity of virus assemblies is an anaphase result of HCMV infection. An HCMV genome has 3 morphological transforming regions inducing cell transformation, namely mtr I, mtr II and mtr III. The mtr I is positioned on the E fragment of Hind III at the tail end of the left side of an ADI69 strain genome U, has the length of 588 bp and can be used for transforming NIH3T3 and primary rat embryo cells. The mtr II is positioned on the Xbal/Bam HI EM fragment of DNA from an HCMV Towne strain, has the length of 980 bp and can transform NIH3T3 and rat-2 cells; ADI69 and TdCMv Tanaka strains of the HCMV have areas corresponding to the strains which contain 2 separated promoters, P1 and P2; and all the transformed cells and tumor cells formed therefrom exist in the mtr II. The mtr III is positioned on an Xbal/BamHI segment, and can be used for encoding main immediate early protein with the molecular weight of 72 kD; the protein is related to trans-activation and auto-regulation of viruses; and the mtr III does not exist in transformed cells.
From the view of cellular levels, infection is divided into three kinds: a. toxigenic infection; b. latent infection; and c. cell transformation or latent carcinogenic infection. The HCMV from an in-vitro test can form a cell strain with virus antigens after being inoculated to a human fibroblast, and has the characteristics of transformed cells. Transfection cells can be extracted from a specific fragment of HCMV-DNA; and partial cells can be integrated to cell chromosome DNA through DNA to transform and are inoculated to an athymic naked mouse to generate tumors. An HPV immortalized human cervical epithelial cell line established by applying HCMV IE transfection through Chaoqi Liu and the like gets the result that the HCMV can promote malignant transformation of cervical epithelial cells in cooperation with HPV16 and form the tumors in the naked mouse after being integrated into a cell chromosome, which explains the close relationship between the HCMV and cervical cancers. The HCMV inactivated by using ultraviolet rays through Deyin Lu and the like is inoculated to the cervical part of the mouse for 3 times per week, totally 8 weeks. Results show that an HCMV group has the cervical precancerous lesion rate of 27.8% (23/83) and the cancer incidence rate of 20.5% (17/83).
Cytomegalovirus (CMV) has a typical herpes virus morphology, with a DNA structure being similar with that of HSV but 5% larger than that of the HSV. The virus has high species specificity from hosts or culture cells. The HCMV can only infect humans and proliferate in human fibroblasts. Viruses proliferate slowly in cell culture, have a long replicative cycle, and can generate cytopathic effects after 30-40 days during primary segregation. The CMV is characterized by cell swelling and rounding, nucleus enlarging and a large acidophilic inclusion body rounded by a “Halo” in a nucleus. The cellular immune function of an organism plays an important role in the generation and development of CMV infection. People with cellular immunity deficiencies can be subjected to serious CMV infection for a long term, as well as further inhibition on the cellular immunity of the organism, such as activity decrease of cytotoxic T cells, functional reduction of NK cells and the like. The organism can generate specific antibodies and cytotoxic T lymphocytes after primary infection from the CMV to activate NM cells. The antibodies have the capacity of limiting CMV replication as well as a certain resistance to reinfection from the same strain but cannot resist to the excitation of endogenous latent viruses and exogenous infection from other different strains of the CMV. However, the cells can give play to the maximum antiviral effect through the toxicity of specificity cytotoxic T lymphocytes and antibody-dependent cells.
The HCMV infection is very common in a crowd, and can cause various diseases. Adult infection is caused frequently in the states of immune deficiencies or immune inhibition. Particularly, the HCMV infection is very easily caused frequently after immunosuppressive agent treatment is received during organ transplantation and bone marrow transplantation as well as malignant tumor patients receive radiotherapy and chemotherapy. AIDS patients are extremely high in the morbidity of the HCMV infection. The HCMV infection is highly valued worldwide due to universality and possible serious consequences, which has a very important significance for the fundamental research of epidemiology, diagnostic techniques, treatment and prevention as well as related virology about the HCMV infection. The immunologic function of tumor patients is greatly lower than that of normal persons after the receiving of the chemotherapy or the radiotherapy. Latent HCMV is easy to reactivate to cause serious infection, which is an important infection factor of influencing the survival rate and the living quality of the tumor patients.
CMV infection disease is congenital or acquired infection caused by the CMV. In the congenital or acquired infection caused by the CMV, the CMV is a double-stranded DNA virus which belongs to a herpes virus group and has a form similar to that of other herpes viruses as well as obvious species specificity from the hosts or tissue culture cells. The HCMV can only be separated and cultured in human embryo fibroblasts.
The HCMV infection is very wide in the crowd. The infection rate of adults in China reaches over 95%. The adult infection is caused frequently in the states of the immune deficiencies or the immune inhibition. Particularly, the HCMV infection is very easily caused frequently after the immunosuppressive agent treatment is received during organ transplantation and bone marrow transplantation as well as the malignant tumor patients receiving the radiotherapy and the chemotherapy. Most of infected persons do not have clinical symptoms, but serious diseases can be generated by affecting multiple organs and systems under a certain condition. The viruses can invade lungs, livers, kidneys, salivary glands, mammary glands and other glands as well as multinuclear leukocytes and lymphocytes, can be excreted from saliva, human milk, sweat, blood, urine, sperm, uterine secretion and other parts for a long term or at intervals, and are usually spread by oral cavities, genital tracts, placentas, blood transfusion or the organ transplantation and other ways.
(I) Congenital infection: the HCMV infection of pregnant maternal bodies can invade fetuses through placentas to cause the congenital infection and a small amount of premature birth, abortion, stillbirth or postnatal death. Child patients can suffer from jaundice, hepatosplenomegaly, thrombocytopenic purpura and hemolytic anemia. Survived children usually leave over permanent mental retardation, neuromuscular dyskinesia, deafness, chorioretinitis and the like.
(II) Perinatal infection: the HCMV is excreted by urinary tracts and cervices of parturients, then infants can be infected through birth canals during childbirth, most of which has slight symptoms or subclinical infection without clinical symptoms and some of which has slight respiratory tract obstacles or liver function impairments.
(III) Children and adult infection: a subclinical type is usually caused by the infection of milk absorbing, kisses, sexual contact, blood transfusion and the like, which may also cause negative mononucleosis of heterophil antibodies sometimes. The viruses hidden in monocytes and the lymphocytes can be activated by receiving immunosuppressive therapy, the organ transplantation, tumors and other factors during pregnancy, which can cause mononucleosis, hepatitis, interstitial pneumonia, retinitis, encephalitis and the like.
(IV) Cell transformation and possible carcinogeneses: fibroblasts of rodent embryos can be transformed by the HCMV inactivated by the ultraviolet rays. The HCMV in certain tumors such as cervical cancer, colon cancer, prostate cancer and kaposis sarcoma is high in the detection rate of DNA and has the antibody titer higher than that of normal persons. Virus particles are also discovered in cell strains established by the tumors, to prompt that the HCMV has potential carcinogenic possibilities the same as herpes viruses of the HCMV. The immunologic function of the tumor patients is greatly lower than that of the normal persons after the receiving of the chemotherapy or the radiotherapy. The latent HCMV is easy to reactivate to cause the serious infection, which is the important infection factor of influencing the survival rate and the living quality of the tumor patients.
Most of HCMV infected patients are in a state of latent infection, so that asymptomatic infection can be avoided frequently even if the HCMV has duplicate activities in vivo. At present, effective and safe anti-HCMV medicines are not available, so the treatment of the HCMV infection is still limited to expectant treatment during symptomatic infection; ganciclovir can only be cautiously used for symptomatic infection because of myelosuppression and other toxic or side effects. Ganciclovir DHPG has an effect of preventing the HCMV from diffusing, and can reduce the death rate of HCMV pneumonia complications of the bone marrow transplantation if being used together with high-titer anti-HCMV immune globulin. Foscarnet sodium can be selected for the HCMV infection resisting to the Ganciclovir DHPG, and has an effect lower than that of the Ganciclovir DHPG although the diffusion of the HCMV can be reduced permanently. HCMV live viral vaccines developed abroad can induce antibody production, but the problem of excluding the oncogenic potential of the vaccines needs to be solved.
Panax ginseng C. A. Mey. (i.e. Ginseng), a traditional Chinese medicine, is a precious medicinal material. Ginsenoside, as a main active ingredient of the ginseng, is widely researched and used. In the ginsenoside, ginseng extracts and derivatives thereof are the most impressive. As the main active ingredient of the ginseng, the ginsenoside with good safety has been prepared into anti-tumor oral preparations applied clinically, and been researched deeply as an injection.
Due to the adoption of an advanced separation and purification technology, the inventor extracts the ginseng extracts and the derivatives thereof serving as active ingredients for treating the HCMV infection, from a ginseng medicinal material, by a large quantity of modern scientific researches, and carries out pharmacodynamical and pharmacological research for treating the HCMV infection on the ginseng extracts and the derivatives and corresponding medicinal preparations thereof. Results prove that the ginseng extracts and derivative monomers thereof have clear pharmacological effects, a strong effect of treating the HCMV infection, low toxic or side effects and high safety, and can provide an efficient low-toxicity medicine for treating the HCMV infection.